Free radical biology for medicine: learning from nonalcoholic fatty liver disease

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Analogs in the treatment of chronic hepatitis B: real life experience with tenofovir and entecavir

INTRODUCTION: Tenofovir and entecavir are potent antiviral agents. By suppressing viral replication, they induce histological improvement and finally delay the progression of chronic hepatitis B and the development of complications. They are rarely associated with serious side effects. Our data from a real life experience support data from the literature and suggest some minimal difference that may be useful in tailoring therapy.PATIENTS AND METHODS: We retrospectively analyzed 54 patients affected by chronic hepatitis B (31 and 23 treated by entecavir and tenofovir, respectively). Eight patients were cirrhotic. At baseline and 4-12 and 24 weeks after starting therapy, biochemical and virological analysis were performed in all patients. Renal function tests (serum creatinine, creatinine clearance and blood urea), serum (calcium and phosphate blood level) and urine electrolyte were also studied.RESULTS: All the patients reached virological control within 24 weeks. Only in the group treated by tenofovir we observed a complete viral suppression within 12 weeks. Some patients treated with tenofovir showed increased creatinine clearance without serum creatinine alteration. No significant side effects were reported with the exception of one case of persistent headache in the entecavir group for which the drug was suspended.CONCLUSIONS: Entecavir and tenofovir are effective in suppressing viral replication in patients with chronic hepatitis B. Tenofovir is more potent than entecavir and viral replication is blocked within 12 weeks of therapy. Tenofovir administration is associated with slight increase of creatinine clearance without alteration of serum creatinine levels. The choice of one or the other should be made according to target and specific patients characteristics. In patients with high serum viral load where the complete and quick control of viral replication is the main target, tenofovir may represent the best choice

Two-Dimensional Shear Wave Elastography Versus Transient Elastography: A Non-Invasive Comparison for the Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C

In recent years, several non-invasive methods have been developed for staging liver fibrosis in patients with chronic hepatitis C. A 2D-Shear wave elastography (SWE) technique has been recently introduced on the EPIQ 7 US system (ElastQ), but its accuracy has not been validated in patients with chronic hepatitis C virus (HCV) infection. We enrolled 178 HCV patients to assess their liver fibrosis stage with ElastQ software using transient elastography as a reference standard. The best cut-off values to diagnose ≥ F2, ≥ F3, and F4 were 8.15, 10.31, and 12.65 KPa, respectively. Liver stiffness values had a positive correlation with transient elastography (r = 0.57; p < 0.001). The area under the receiver operating characteristics (AUROC) was 0.899 for ≥ F2 (moderate fibrosis), 0.900 for ≥ F3 (severe fibrosis), and 0.899 for cirrhosis. 2D-SWE has excellent accuracy in assessing liver fibrosis in patients with chronic hepatitis C and an excellent correlation with transient elastograph

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

Direct‐acting antivirals for HCV treatment in older patients: A systematic review and meta‐analysis

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Risk of Statin-Induced Hypertransaminasemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective: To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia. Patients and methods: We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration. Results: Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; P<.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; P<.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; P=.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; P=.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo. Conclusions: A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin

Ocular involvement in Behçet's Disease: relevance of new diagnostic tools

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DIRECT-ACTING antivirals restore systemic redox homeostasis in chronic HCV patients

Chronic hepatitis C therapy has completely changed in the last years due to the availability of direct-acting antivirals (DAAs). Removing the virus may be not enough since chronic infection deeply modifies immune system and cellular metabolism along decades of inflammation. Oxidative stress plays a significant role in maintaining systemic inflammation during chronic HCV infection. Other than removing the virus, effective therapy could counteract oxidative stress. This study investigated the impact of DAA treatment on circulating markers of oxidative stress and antioxidant defence in a cohort of patients affected by chronic hepatitis C. To this, an observational study on 196 patients who started therapy with DAA for HCV-related hepatitis was performed. Patients were assessed at baseline, 4 weeks after the initiation of therapy (4wks), at the end of treatment (EoT), and 12 weeks after the EoT (SVR12). Circulating oxidative stress was determined by measuring serum hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and 8-hydroxydeoxyguanosine (8-OHdG). Antioxidant status was evaluated by measuring the enzymatic activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in peripheral blood mononuclear cells. We observed a reduction of serum 8-OHdG at 4wks, while the circulating level of both HNE- and MDA-protein adducts diminished at EoT; all these markers persisted low at SVR12. On the other side, we reported an increase in the enzymatic activity of all the antioxidant enzymes in PBMC at EoT and SVR12. Taking into account circulating 8-OHdG and antioxidant enzyme activities, patients with high fibrosis stage were those that had the most benefit from DAA therapy. To conclude, this study indicates that treatment with DAAs improves the circulating redox status of patients affected by chronic hepatitis C. This positive impact of DAA therapy may be related to its effectiveness on cutting down viremia and pro-inflammatory markers

The GLP-1 receptor agonist Exendin-4 modulates hippocampal NMDA-receptor signalling in aged rats and improves cognitive impairment in diabetic elderly patients

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